Renal catabolism of advanced glycation end products: the fate of pentosidine.
Advanced glycation end products (AGEs) generated through the Maillard reaction significantly alter protein characteristics. Their accumulation has been incriminated in tissue injury associated with aging, diabetes, and renal failure. However, little is known about their clearance from the body. The present study delineates the catabolic pathway of a well-defined AGE product, pentosidine. Synthesized pentosidine given intravenously in rats with normal renal function was rapidly eliminated from the circulation through glomerular filtration, but was undetectable in the urine by chemical analysis. Immunohistochemistry with anti-pentosidine antibody disclosed that pentosidine accumulated transiently in the proximal renal tubule one hour after its administration, but had disappeared from the kidney at 24 hours. After an intravenous load of radiolabeled pentosidine, radioactivity peaked in the kidney at one hour and subsequently decreased, whereas it rose progressively in the urine. Over 80% of the radioactivity was recovered in the 72-hour collected urine. However, only 20% of urine radioactivity was associated with intact pentosidine chemically or immunochemically. In gentamicin-treated rats with tubular dysfunction, up to 30% of the pentosidine load was recovered as intact pentosidine in the urine. The present study suggests that free pentosidine (and possibly other AGEs) is filtered by renal glomeruli, reabsorbed in the proximal tubule where it is degraded or modified, and eventually excreted in the urine. Kidney thus plays a key role in pentosidine disposal.
Miyata
T
T
Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Ueda
Y
Y
Horie
K
K
Nangaku
M
M
Tanaka
S
S
van Ypersele de Strihou
C
C
Kurokawa
K
K
D000818:Animals; D000900:Anti-Bacterial Agents; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005839:Gentamicins / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000652:urine; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D017127:Glycation End Products, Advanced; D011500:Protein Synthesis Inhibitors; D001120:Arginine; C062187:pentosidine; D008239:Lysine